Bioactivity profiling and mode of action studies of antibacterial and antibiofilm agents of marine origin

The emergence of drug-resistant strains and new pathogens intensifies the need for new antimicrobials. Additionally, bacterial biofilms, which contribute to persistent infections, further complicate treatment efforts. The increasing difficulty in discovering and developing new antimicrobials adds to this challenge. However, marine environments, with their vast biodiversity, offer a promising avenue for antibiotic discovery, particularly through natural products synthesized by marine microorganisms. These organisms are a rich source of novel bioactive secondary metabolites with potential therapeutic applications. Additionally, synthetic mimics of antimicrobial peptides represent another promising direction in the quest for new antimicrobials. Paper I elucidate the structure-activity relationship of cationic amphipathic N,N'-dialkylated-5,5-disubstituted barbiturates as marine eusynstyelamide mimics, investigating their potential as antimicrobial agents. The library of 58 compounds, synthesized through a strategic approach, demonstrated the significance of cationic groups, hydrocarbon linkers, and lipophilic side chains on antimicrobial and haemolytic activities. Notably, guanidyl and amine groups showed broad-spectrum activity, while trimethylated quaternary amines were more selective for Gram-positive bacteria. The compounds, especially 11lG, 13jA, and 13jG, showed potent antimicrobial effects with low haemolytic activity, with the guanidine derivative 11lG significantly disrupting bacterial membranes. In paper II, the investigation into tetrasubstituted, cationic, amphipathic heterocycles as antimicrobial peptide (AMP) mimics identified hydantoin as a favourable scaffold, influencing haemolytic activity and antimicrobial potency. Among the hydantoin derivatives studied, three leads (2dA, 6cG, and 6dG) exhibited promising broad-spectrum activity, with 6dG showing notably low minimum inhibitory concentration values. The mode of action studies revealed a pronounced membranolytic effect on the inner and outer bacterial membranes, emphasizing the importance of structural arrangement in AMP mimics. In paper III, the antibiofilm capabilities and in vivo efficacy of these peptidomimetics were explored using a zebrafish model, discovering that 13iA and 2cA presented remarkable biofilm inhibition and eradication potentials, along with moderate activity against resistant clinical isolates. Their lack of toxicity, immunogenicity, and promising in vivo antibacterial activity in the zebrafish model up to 16 mg/kg dose showcases their potential as templates for new antibiotics against antimicrobial resistance (AMR). In paper IV, the bioprospecting work focused on Arctic marine bacterial isolates from various habitats near Tromsø and towards the North Pole indicated the presence of biosynthetic gene clusters (BGCs) with antimicrobial activity. Of the 158 isolates, 65 exhibited antibacterial activity, and 37 confirmed the presence of nonribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) BGCs, with genome sequencing and mining unveiling multiple BGCs. Seven of these isolates displayed activity against both Gram-positive and Gram-negative pathogens and contained NRPS or PKS BGCs, advancing them as promising sources of novel antimicrobial agents. These combined efforts contribute valuable insights into the design and discovery of new antimicrobials, addressing the urgent global challenge of AMR with innovative solutions derived from marine bioprospecting and synthetic peptidomimetic chemistry.Fremveksten av antibiotika-resistente bakteriestammer og nye patogener øker behovet for nye antimikrobielle midler. Bakterier som danner biofilm kompliserer dette ytterligere da biofilm bidrar til vedvarende infeksjoner som er utfordrende å behandle. Marine miljøer representerer et enormt biologisk mangfold og unike naturstoffer som kan være et lovende utgangspunkt for å oppdage nye antibiotiske forbindelser. Særlig de marine mikroorganismene representerer en rik kilde til nye bioaktive sekundære metabolitter som kan ha mulige terapeutiske anvendelser. Dersom vi er i stand til å lage syntetiske etterligninger av for eksempel antimikrobielle peptider (AMP), representerer dette en annen lovende retning i utviklingen av nye antibiotika. Artikkel I belyses sammenhengen mellom struktur og aktivitet til kationiske amfipatiske N,N'-dialkylerte-5,5-disubstituerte barbiturater som etterligner marine eusynstyelamider, og ser på deres potensial som antimikrobielle midler. Testing av et bibliotek bestående av 58 syntetiserte forbindelser, demonstrerte betydningen av ulike kationiske grupper, hydrokarbon-bindinger og lipofile sidekjeder for den antimikrobielle og hemolytiske aktiviteten. Spesielt viste forbindelser med guanidyl- og aminogrupper en bredspektret aktivitet, mens trimetylerte kvarternære aminer var mer selektive for Gram-positive bakterier. Særlig forbindelsene 11lG, 13jA og 13jG, viste potente antimikrobielle effekter og samtidig en ønskelig lav hemolytisk aktivitet. Guanidinderivatet 11lG viste signifikant ødeleggelse av bakterielle membraner. I artikkel II, undersøkes det om nye AMP-analoger påvirker den hemolytiske og antimikrobielle aktiviteten. Dette ble utført ved å syntetisere en kombinasjon av tetrasubstituerte, kationiske, amfipatiske heterosykler som hydantoin-strukturer. Av hydantoin-derivatene som ble studert, gav tre forbindelser (2dA, 6cG og 6dG) best lovende bredspektret aktivitet, mens 6dG viste lavest minimale hemmende konsentrasjonsverdier. Virkningsmåtestudier avslørte at romlig arrangement av de kjemiske komponentene i strukturen på AMP-etterligningene hadde avgjørende betydning for lytisk effekt på både de indre og ytre bakteriemembranene. I artikkel III ble antibiofilmegenskapene og in vivo-effektiviteten til disse peptidomimetikaene utforsket ved å bruke en sebrafiskmodell. Da ble det oppdaget at forbindelsene 13iA og 2cA både kunne hemme og fjerne bakteriell biofilm, samtidig som de viste moderat aktivitet mot resistente kliniske bakterieisolater. Stoffenes mangel på toksisitet og immunogenisitet, men samtidig lovende in vivo antibakteriell aktivitet (vist med sebrafiskmodellen), tyder på at deres struktur har et potensial som nye antibiotika mot antibiotika-resistente bakterier. I artikkel IV, kunne vi med bioprospektering på arktiske marine bakterieisolater fra ulike habitater nær Tromsø og mot Nordpolen, vise at disse både hadde biosyntetiske genklynger (BGC) og antimikrobiell aktivitet. Av de 158 isolatene som ble testet, viste 65 antibakteriell aktivitet, 37 hadde gener som kodet for ikke-ribosomal peptidsyntetase (NRPS) eller polyketidsyntase (PKS) BGCs og i tillegg flere typer av BGCer. Syv av disse 158 isolatene viste både aktivitet mot både Gram-positive og Gram-negative patogene bakterier og inneholdt NRPS eller PKS BGCer. Disse stammene representerer dermed lovende utgangspunkt for videre studier for identifiseringen og karakteriseringen av nye antimikrobielle midler. Forskning som kombinerer bruk av ulike teknikker og angriper fra ulike vinkler, bidrar med verdifull innsikt i utformingen og oppdagelsen av nye antimikrobielle stoffer, og kan dermed adressere den globale utfordringen med antimikrobiell resistens med innovative løsninger avledet fra marin bioprospektering og syntetisk peptidomimetisk kjemi

Design and Development of a Segmented Rubbe-tracked Vehicle for Sepang Peat Terrain in Malaysia

The study describes the design and development of a segmented rubber tracked vehicle for operating on unprepared peat terrain. The vehicle was to traverse accurately and reliably on the 18.79k~lmlo~w bearing capacity peat terrain. The study observed four main contributions towards determining the mechanical properties of peat terrain, developing simulation models for optimizing the design parameters of the vehicle, designing and developing the vehicle to be able to traverse accurately on low bearing capacity peat terrain, and designing an innovative instrumentation system on the vehicle for collecting relevant data to measure vehicle tractive performance. An analytical framework for determining the mechanical properties of peat soil in view of predicting the tractive performance of tracked vehicle was presented. It took into account the load-sinkage and shearing characteristics of peat. An experimental study on the mechanical properties of peat was conducted in Sepang, Selangor, Malaysia. The stiffness values of surface mat and underlying weak peat deposit from load-sinkage test were determined by specially made bearing capacity apparatus. The mean values of surface mat stiffness before and after drainage were found to be 31kN/m3 and 46k~lr-n~~ respectively. The mean value of underlying peat stiffness before and after drainage were found to be 252kN/m3 and 380kN/m3, respectively. The mean value of internal frictional angle, cohesiveness and shear deformation modulus of the peat soil sample were determined using a direct shear box apparatus in the laboratory. The mean value of internal frictional angle, cohesiveness and shear deformation modulus of the peat soil before and after drainage were found to be 22.80" and 24.3 lo, 2.63kN/m2 and 2.89kN/m2, and 1.2 1 cm and 1.37cm7 respectively. A new simulation technique for studying the basic design parameters of the vehicle with rigid link tracks system on Sepang peat terrain in Malaysia was also presented. The proper track width, ground contact length, pitch and grouser height, idler diameter and location, sprocket diameter and location, road-wheel diameter and geometrical arrangement, the ratio of the road-wheel spacing to track pitch, location of the center ofgravity (CG) of the vehicle are important to select to ensure good tractive performance of the vehicle on unprepared peat terrain. Simulation technique was then used to optimize the design parameters of the vehicle by establishing mathematical models for the trackterrain interaction mechanism. In the simulation study, the 25.5kN vehicle including payloads of 5.89kN was considered to traverse on the peat terrain at lOkm/h. The simulation study for the vehicle of straight running motion showed that the nominal ground pressure of the vehicle was 23.3% lower than the bearing capacity of the peat terrain. From simulated tractive performance results, vehicle average motion resistance coefficient of 6.8 to 7.9%, drawbar pull coefficient of 25.22 to 47%, and tractive efficiency of 74 to 77%, were found for the slippage of 5 to 20%. For the simulation study on the vehicle of turning motion, the result showed that the vehicle ground contact pressure exit from outer track was 14.61% and from the inner track was 6.67% lower than the bearing capacity of the Sepang peat terrain, the sinkage of the vehicle outer track 10.5% lower and inner track 22.5% lower, torque of the outer track sprocket 7.85% higher than the turning moment resistance of the vehicle, and lateral resistance 7.4% higher than the centrifugal force of the vehicle which was ensured the vehicle to maintain the steady state turn on the Sepang peat terrain at a turning speed of 1 Okm/h. The vehicle field tests were conducted on three different types of peat terrains: Terrain Type I, Terrain Type 11, and Terrain Type I11 with two loading conditions at travel speeds of 6km.h and 10km.h. The results showed that the tractive effort of the vehicle was increased 13.7 1 % for Terrain Type 1, 1 1 .O9% for Terrain Type 11, and 13.53% for Terrain Type I11 when the traveling speed was increased from 6kmh to 10krnIh. From the variation of the vehicle tractive operating environment, it was found that the tractive effort of the vehicle at traveling speed of 6kmih increased 8.08%, 5.12%, and 14.14% for changing the vehicle operating environment from Terrain Type I to Terrain Type 11, Terrain Type I1 to Terrain Twe 111, and Terrain Type I to Terrain Type 111, respectively. Similarly, the tractive effort for the vehicle at a traveling speed of lOkm/h increased 6.32%, 7.42%, and 14.22% for changing the vehicle operating environment from Terrain Type I to Terrain Type 11, Terrain Type I1 to Terrain Type 111, and Terrain Type I to Terrain Type 111, respectively. Furthermore, the tractive effort of the vehicle at a traveling speed of 6kmh increased 2.28% for Terrain Type I, 5.124% for Terrain Type 11, and 6.46% for Terrain Type 111 when the vehicle changing operating loading condition from without payload to with full payload. Similarly, the tractive effort of the vehicle at a traveling speed of 1Okm/h increased 1.76% for Terrain Type I, 2.61% for Terrain Type 11, and 6.69% for Terrain Type I11 when the vehicle changing operating loading condition from without payload to with full payload

Are Credit Unions Just Small Banks? Determinants of Loan Rates in Local Consumer Lending Markets

Only recently have studies of banking markets paid attention to the potential competitive discipline provided by credit unions on consumer loan rates. However, an unresolved issue is the extent to which credit unions are substitutable for banks. We analyze a combined sample of 100 banks and 187 credit union in 68 U.S. markets observed quarterly over the 1992-1998 period, to explain loan rates for two types of consumer loans. Our results suggest that, even after controlling for market shares and deposit sizes of institutions, credit unions charge their members significantly lower interest rates on loans than do banks. Furthermore, an examination of the pattern of responses to lagged interest rates yields an indication of greater inertia in rate-setting by credit unions than by banks.

Performance-based seismic analysis and design improvements of two precast concrete structural systems

This study focuses on the multiple-level seismic performance in terms of structural and non-structural damages of precast hybrid frame and jointed precast post-tensioned wall systems through dynamic analysis of precast buildings subjected to spectrum compatible ground motions of various intensities. The maximum transient interstory drift, residual interstory drift and floor acceleration are considered as acceptance criteria for evaluating seismic performance of these systems subjected by four levels of ground motions. Interstory drift and floor acceleration are directly related to structural and non-structural damages, respectively. Two dimensional non-linear finite element analytical models for hybrid frames and jointed wall systems used in this study are validated against test results for a five story test building. In designing both precast systems, it is shown that traditional force-based design approach results in significantly higher level of design base shear compared to direct displacement-based design approach. After observing satisfactory performance in the five story model building designed by direct displacement-based approach, similar multiple-level seismic performance is evaluated for five, seven and ten story buildings designed by direct displacement-based method. These low to mid-rise full scale precast hybrid frame and jointed precast post-tensioned wall systems also exhibit the maximum transition interstory drift, residual interstory drift and floor acceleration within the acceptable limits, thus it is recommended that these systems may be utilized as primary lateral load resistant structural systems when designed by the economic approach of direct displacement-based design. Influence of variation of heights of buildings on the performance of these systems is also examined

Design and development of UrbanConcept car

The “UrbanConcept” vehicle is defined as a fuel economy pure electrical vehicle which will be the closer in appearance and technology to road-going vehicles, addressing current transportation. Increasing the fuel shortage and hiking the fuel price are made the political un-stability all over the world year-toyear and decade-to-decade. While, the automotive exhaust gas emission has a significant impact on environment. This is problem and big one at this moment. For decades scientists and politicians have struggled with finding solutions to these important problems. From this study it is committed to offer a most fuel-efficient vehicle and to reduce the environmental footprint of its operations and to help meet the world’s growing demand for energy in secure and sustainable ways. To design and build this vehicle is the most challenging to make the vehicle weight below than 200 kg (including 70 kg driver weight). The goal of the project is not to operate with high speed but emphasis is given on the consumption as little fuel as possible over a set distance. Theoretically, it is found that the developed vehicle that travel further using less energy will achieve 1820 km per 1 litre equivalent of fuel. Furthermore, the design and developed vehicle will not only to contribute to the fuel efficiency vehicle, but also incorporate recycled and eco-friendly materials into the vehicle. One particular feature of this vehicle is that the waste power from the braking will be recover from regenerative braking system as the vehicle will follow-up “stop & go” driving. The vehicle will be propelled from the power of hub traction motor which will powered by super capacitor

Suitability of IPO Pricing Methods to Overcome Underpricing: A Comparative Study in Bangladesh

Initial Public Offering (IPO) mechanism gives a part of ownership of companies to small savers and enables investors to contribute to the economic development. This paper explores selected techniques by which companies going to public vary substantially across the world in the most studied market. In Bangladesh, there are two main methods of IPO pricing. One is Fixed Price (FP) method and another is Book Building (BB) method. It is difficult to isolate the impact of book building method relative to fixed price method which is used by the companies to go public. The empirical evidence demonstrates that most of the companies enter into capital market through FP method and BB method is the current issue in the capital market of Bangladesh. This study analyzes the trends of underpricing, overpricing, and oversubscription in initial public offerings (IPOs) listed in Dhaka Stock Exchange (DSE) and to what extent on a year to year basis. After introducing BB method in Bangladesh, 91 companies were listed in DSE during 2008-2015 except mutual fund and bond, out of which 87(95.60%) IPOs were listed through FP method and only 4(4.40%) were listed through BB method, and 89 (97.80%) IPOs were found to be underpriced, only 2 (2.20%) were overpriced while nothing is accurately priced. This research reveals that book building method may diminish the degree of underpricing and also compact the variance of over subscription considering all factors relating to IPOs in Bangladesh. Keywords: IPO, Fixed Price Method, Book Building Method, Primary Market, Underpricing

Thermoelectric technology for IC engine waste energy harvesting: liquid cooling approach

Thermoelectric generators are all solid-state devices that convert heat into electricity. It contains no moving parts and is completely silent. The total heat supplied to the engine in the form of fuel, approximately 30 to 40% is converted into useful mechanical work; whereas the remaining heat is expelled to the environment through exhaust gases and engine cooling systems, resulting in serious environmental pollution. So, it is required to utilize waste heat into useful work. The technologies on waste heat recovery of exhaust gas from internal combustion engines (ICE) are invented as thermo electric generators (TEG) with finned type, Organic Rankine cycle (ORC) and Turbocharger. This paper has presented semi-conductive TEG and GO/Silica composite TEG. Finned and liquid cooling type cooling has been adopted in both of the TEG. The performance of both cooling approaches for semi-conductive TEG has been compared in experimentally for the engine speed in the range 1000-3000 rpm. The result shows that the liquid cooling TEG has 25% higher performance in terms of electric power generation than the finned type TEG. The liquid cooling TEG has exhibited higher performance at engine speed of 5000 rpm and it was developed 524 W which can be used to operate the air-condition system of the vehicle, could contribute to reduce the 7-10% of engine total fuel consumption and improve emission level by 7%

Performance investigation of an advanced tracked prime mover on the low bearing soil

This study has presented a performance investigation of an advanced tracked prime mover for the operation of agricultural goods and other operations on peat terrain. The maximum and continuous traction torque of the prime mover has been developed by designing an advanced controller for controlling the intelligent system. The prime mover’s mobility is studied with ultrasonic displacement sensor, torque transducer, National Instrument cRIO-9004 Compact-RIO Real-time Controller Unit (RCU), a National Instrument TPC 2106T Touch Panel Control (TPC), a Trimble AG132 GPS antenna and receiver unit, and a Dlink DIR-655 router. The fuzzy logic controller (FLC) has been equipped with the prime mover hydraulic system to increase the traction torque of the hydraulic motor when the prime mover’s sinkage is more than or equal to 70 mm. The prime mover’s design demonstrates good potential in traversing peat terrain as the measured tractive effort was found to be 48% of the vehicle’s gross weight while the recommended tractive effort is in the range of 30–36% of the vehicle’s gross weight

Rethinking the I/O Stack for Persistent Memory

Modern operating systems have been designed around the hypotheses that (a) memory is both byte-addressable and volatile and (b) storage is block addressable and persistent. The arrival of new Persistent Memory (PM) technologies, has made these assumptions obsolete. Despite much of the recent work in this space, the need for consistently sharing PM data across multiple applications remains an urgent, unsolved problem. Furthermore, the availability of simple yet powerful operating system support remains elusive. In this dissertation, we propose and build The Region System – a high-performance operating system stack for PM that implements usable consistency and persistence for application data. The region system provides support for consistently mapping and sharing data resident in PM across user application address spaces. The region system creates a novel IPI based PMSYNC operation, which ensures atomic persistence of mapped pages across multiple address spaces. This allows applications to consume PM using the well understood and much desired memory like model with an easy-to-use interface. Next, we propose a metadata structure without any redundant metadata to reduce CPU cache flushes. The high-performance design minimizes the expensive PM ordering and durability operations by embracing a minimalistic approach to metadata construction and management. To strengthen the case for the region system, in this dissertation, we analyze different types of applications to identify their dependence on memory mapped data usage, and propose user level libraries LIBPM-R and LIBPMEMOBJ-R to support shared persistent containers. The user level libraries along with the region system demonstrate a comprehensive end-to-end software stack for consuming the PM devices

How Vulnerable are Bangladesh’s Indigenous People to Climate Change?

This paper compares the vulnerabilities to climate change and climate variability of the indigenous people with the Bengali population of Bangladesh. It distinguishes between (a) individual vulnerabilities that are related to an individual’s capability to adapt to climate change and; (b) spatial vulnerabilities, that is, vulnerabilities that are related to the location of a person (like the exposure to climate change-induced disasters). While an individual’s capability to adapt to climate change is determined by many factors, some relatively simple approximation is to look at poverty, landlessness, and illiteracy. Spatial vulnerabilities are reviewed by looking at drought hazard maps, flood hazard maps, landslide hazard maps, and cyclone hazard maps. Hence, the paper compares levels of poverty, landlessness, illiteracy, and the more direct though also more subjective exposures to increased droughts, floods, landslides, and cyclones across the two population groups. The paper concludes with some broad suggestions on adaptation strategies of indigenous people as well as suggestions for policy interventions to reduce climate change-induced vulnerabilities for indigenous people in the Chittagong Hill Tracts (CHT).Bangladesh, climate change, vulnerability